From the background to the spotlight: TASK channels in pathological conditions

Brain Pathol. 2010 Nov;20(6):999-1009. doi: 10.1111/j.1750-3639.2010.00407.x.

Abstract

TWIK-related acid-sensitive potassium channels (TASK1-3) belong to the family of two-pore domain (K(2P) ) potassium channels. Emerging knowledge about an involvement of TASK channels in cancer development, inflammation, ischemia and epilepsy puts the spotlight on a leading role of TASK channels under these conditions. TASK3 has been especially linked to cancer development. The pro-oncogenic potential of TASK3 could be shown in cell lines and in various tumor entities. Pathophysiological hallmarks in solid tumors (e.g. low pH and oxygen deprivation) regulate TASK3 channels. These conditions can also be found in (autoimmune) inflammation. Inhibition of TASK1,2,3 leads to a reduction of T cell effector function. It could be demonstrated that TASK1(-/-) mice are protected from experimental autoimmune inflammation while the same animals display increased infarct volumes after cerebral ischemia. Furthermore, TASK channels have both an anti-epileptic as well as a pro-epileptic potential. The relative contribution of these opposing influences depends on their cell type-specific expression and the conditions of the cellular environment. This indicates that TASK channels are per se neither protective nor detrimental but their functional impact depends on the "pathophysiological" scenario. Based on these findings TASK channels have evolved from "mere background" channels to key modulators in pathophysiological conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Brain Diseases / classification
  • Brain Diseases / genetics*
  • Brain Diseases / pathology*
  • Disease Models, Animal
  • Humans
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Potassium Channels, Tandem Pore Domain / genetics*
  • Potassium Channels, Tandem Pore Domain / metabolism

Substances

  • Nerve Tissue Proteins
  • Potassium Channels, Tandem Pore Domain
  • potassium channel subfamily K member 3